Colorectal cancer (CRC) is the second leading cause of cancer death in the U.S. Colonoscopy is widely used to screen for CRC. Current guidelines recommend screening colonoscopy once every 10 years in average risk patients over >50 year who have no polyps identified at colonoscopy (i.e., negative colonoscopy). However, the prevalence of CRC and polyps increase with age. In addition, nearly 1/4 of the U.S. population over 60 years of age have diabetes mellitus (DM). Recent data suggest patients with diabetes mellitus (DM) have an increased risk of CRC. Furthermore, population-based cancer incidence data have consistently suggested a higher incidence of CRC among men vs. women, and the disparity is most striking among those >65 years. Hence, the negative predictive value of a negative colonoscopy may be lower in patients >65 years who are male or have DM. As a result, there is uncertainty whether the recommended 10-year interval between screening colonoscopies in whom no polyps were identified should apply to elderly men or elderly DM patients. We hypothesize that among patients over the age of 65, the risk of CRC following a negative colonoscopy is higher in men vs. women, and in DM patients vs. non-DM patients. To test this hypothesis, we have designed a population-based cohort study using the linked SEERMedicare data. The study will determine among the SEER-Medicare population, 1) whether men who have undergone a negative colonoscopy have a higher subsequent incidence of CRC than women with a negative colonoscopy;2) whether DM patients who have undergone a negative colonoscopy have a higher subsequent incidence of CRC than non-DM patients with a negative colonoscopy;3) whether men or DM patients who have undergone a negative colonoscopy have a lower incidence of CRC than the general SEER-Medicare population who have not undergone colonoscopy and whether the lower incidence persists for up to 10 years;4) determine the absolute incidence by time of CRC following a colonoscopy without polyps for men, women, all patients with diabetes, men with diabetes, and women with diabetes. Both relative and absolute risks will be examined during the follow-up period. Subgroup analysis will examine the risk for proximal colon cancer and the combined effect of male sex and DM. Relevance to Public Health: CRC is a common cause of death among the elderly population. Screening for colorectal cancer can reduce the risk of cancer and cancer-related mortality. Given the increased incidence of CRC in elderly male patients or elderly DM patients, it is important to determine whether the recommended 10-year interval between colonoscopies without polyps offers adequate protection to these high risk groups. Our study will help establish the appropriate time interval for elderly men and elderly DM patients to undergo a second colonoscopy following a negative colonoscopy so that they will not be facing an unacceptably high rate of preventable CRC morbidity and mortality.